The objective of the proposed research is to delineate the nature and time course of molecular events occurring in hemopoietic cells during erythroid differentiation and replication. This will increase knowledge of regulatory mechanisms on a basic level. It will at the same time supply information necessary for attempts at modification and control of both differentiation and replication of such cells having undergone neoplastic transformation (leukemias, certain solid tumors). The hormonal agent erythropoietin, non-hormonal regulators such as nucleoside 3'-5' cyclic monophosphates, prostaglandins, chalone and antichalone-like factors, estrogens and androgens, all known or at least suspected to have a direct regulatory effect on cells in the course of erythroid differentiation, will be employed to manipulate differentiation and replication at will both in vivo and in cell cultures. Pertinent observations will be made on isolated subcellular systems such as nuclei, chromatin, membranes, etc. It will be attempted to develop sub-cellular systems in which at least certain parts of the differentiation and/or replication processes can also be induced in vitro. Radioactively labeled compounds will be used to study the synthesis and binding properties of macromolecules of interest. Cell separation techniques directed towards the above objectives will be utilized and further developed.